Abstract 4908: Study on Ca 2+-mediated regulation mechanisms on chemotherapy-induced peripheral neuropathy in multiple myeloma and non-Hodgkin lymphoma
Authors: Jinny Park, Jong-Suk Kim, Kwang-Hyun Park
Journal: Cancer Research (2023)

Abstract In general, when treating cancer patients, various anticancer drugs are used in combination to enhance the anticancer effect. However, most drugs exhibit side effects. Neurotoxicity, one of the side effects commonly accompanied, greatly affects the quality of life and also reduces compliance with treatment. Calcium signal transduction, which occupies a key position in cell signal transduction, has been found to be involved in various mechanisms including proliferation, differentiation, and death of cells, beyond the existing research direction that focuses on channels. To identify the mechanisms of calcium signal regulation that can reduce chemotherapy induced peripheral neuropathy (CIPN) while maintaining anticancer functions of drugs, we study with the two drugs frequently used in non-Hodgkin lymphoma and multiple myeloma, borteozomib (BTZ) and vincristine (VIN), whose main side effects are neurotoxicity. We used the human neuroblastoma cell line, SH-SY5Y cells, and performed MTT assay after treating them with N-Acetylcysteine ​​(NAC), an antioxidant, to determine whether the reduction in cell viability by BTZ and VIN was due to the increase in ROS. When BTZ and VIN were treated with NAC, cytotoxicity by BTZ was significantly reduced and cell viability decreased by VIN was significantly increased. From these results, we found that ROS are involved in BTZ and VIN -induced apoptosis. In addition, we performed MTT assay using calcium inhibitors to investigate whether intracellular calcium signaling is involved in BTZ and VIN-induced apoptosis, and 8-Br-cADPR, Ned-19, Xestospongin C, and Heparin were used as calcium inhibitors. To confirm that the cell viability reduced by BTZ and VIN is recovered by calcium inhibitors, BTZ and VIN were treated together with calcium inhibitors, respectively. Cell viability was found to increase significantly. These results suggest that intracellular calcium signaling is involved in cell death induced by BTZ and VIN. The increase in [ca2+]i in the cytoplasm when treated with BTZ and VIN was measured using a fluorescence spectrophotometer. It was shown that the treatment with BTZ and VIN increased the calcium concentration in the cytoplasm within 1 minute. To confirm that the concentration of intracellular calcium was reduced by the calcium inhibitor, BTZ and calcium inhibitor were treated together, and it was confirmed that the intracellular calcium concentration increased by BTZ was decreased in a concentration-dependent manner at 2uM and 3uM of the calcium inhibitor. In conclusion, this experiment suggests that intracellular calcium signaling is involved in the BTZ and VIN’s reduction of neuronal cell viability (CIPN) in multiple myeloma and non-Hodgkin lymphoma. This research was supported by NRF 2021R1A2C1091322 (J.-S.Kim) and 2021R1F1A1064120 (J. Park). Citation Format: Jinny Park, Jong-Suk Kim, Kwang-Hyun Park. Study on Ca 2+-mediated regulation mechanisms on chemotherapy-induced peripheral neuropathy in multiple myeloma and non-Hodgkin lymphoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4908.